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Medical Cell Biology

by Xiaoying Liu
E-mail: 1123796489@qq.com
Textbook & Reference book
Introduction to Cell Biology

Outline
◆ Overview of Cell Biology;
◆ The History of Cell Biology;
◆ Cell Biology and Medicine.
Cell biology (cytobiology)
Cell biology is a branch of biology that studies the
different structures and functions of the cell and focuses
mainly on the idea of the cell as the basic unit of life.

Cellular level (microscopic level)


---- by light microscope
Subcellular level (submicroscopic→ level)
---- by electron microscope
Molecular level
Three levels of cytobiology

Microscopic
level

Submicroscopic
level

Molecular
level
Three levels of cytobiology (e.g. human skin)

Living systems such as the human body consist of closely interrelated elements.
Adhesion belt

7
Macromolecular assembly
A sense of scale between living cells and atoms

9
Resolving power

?
The resolving power of
our naked eyes, light
microscope and
electron microscope?
2. Main contents of cell biology

Structures and Functions

nucleus and
membrane organelles skeleton
chromesome

signal proliferation differenation & senescence


transduction & regulation stem cell biology & death

Cytogenetics Cytophysiology Cytosociology Membrane biology

Chromosome biology Genomics Proteomics


Section 2. The History of Cell Biology
1. The discovery of cells followed from the
invention of the microscope.

Robert Hooke - Wikipedia, the free encyclopedia


In 1665, Robert Hooke saw a network of tiny boxlike
compartments that reminded him of a honeycomb. He
called these little compartments “cellulae”, a Latin term
meaning little room. It is from this word we get our
present-day term, cell.
Anton van the first practical
Leeuwenhoek microscopes
In 1674, Dutchman Leeuwenhoek: “the Father of Microbiology”, and
considered to be the first microbiologist, best known for his work
on the improvement of the microscope.

Antonie van Leeuwenhoek - Wikipedia, the free encyclopedia


2. Cell theory
Matthias Jakob, Schleiden
(1804-1881)
German botanist

Theodor Schwann (1810-1882),


German physiologist and histologist

Rudolf Virchow (1821-1902), German


doctor, anthropologist, pathologist,
prehistorian, biologist and politician
Cell theory - Wikipedia, the free encyclopedia
Three basic tenets of cell theory
⚫ All organisms are
composed of one or
more cells.
⚫ The cell is basic unit
of structure and
organization in
organisms.
⚫ All cells arise only from
pre-existing cells by
division.
Modern interpretation of Cell Theory
The generally accepted parts of modern cell theory include:
1. All known living things are made up of one or more cells.
2. All living cells arise from pre-existing cells by division.
3. The cell is the fundamental unit of structure and function
in all living organisms.
4. The activity of an organism depends on the total activity
of independent cells.
5. Energy flow (metabolism and biochemistry) occurs within
cells.
6. Cells contain DNA which is found specifically in the
chromosome and RNA found in the cell nucleus and
cytoplasm.
7. All cells are basically the same in chemical composition
in organisms of similar species.
The modern version of Cell Theory

1. Energy flow occurs within cells.


2. Heredity information (DNA) is passed on
from cell to cell.
3. All cells have the same basic chemical
composition.
The cell is the structural unit of life, all
organisms are made up of cells.
3. The classical cytology

1. Protoplasm theory.
1861, by Max Schultze.
The cell was a container for protoplasm, the
fundamental and universal material
substance of life.
The classical cytology
The chicken embryo blood cells
1841,R.Remark amitosis

Fixation and dyeing


1882,W.Flemming mitosis
Centrosome, mitochondrion and Golgi apparatus
were found.
1876, O.Hertwig meiosis
4. Experimental cytology
1892, O. Hertwig:《Zelle und Gewebe》(《Cell and Tissue》).

cytogenetics cytophysiology cytochemistry

O. Hertwig; R.Harrison & R.Feulgen;


G. Mendel; A.Carrel; J.Brachet;
T.H.Morgan. A.Claude. T.Casperson.
Thomas Hunt Morgan (1866-1945)

In 1908, T. H. Morgan started working on the fruit fly


Drosophila melanogaster;
In 1910 Morgan noticed a white-eyed mutant male among
the red-eyed wild types.
In 1911, he concluded that:
(1) some traits were sex-linked,
(2) the trait was probably carried on one of the sex
chromosomes, and
(3) other genes were probably carried on specific
chromosomes as well.
The three cornerstones of cell biology

Cell theory

Theory of evolution Modern biology

Theory of heredity
5. Cell biology
1931,M.Knoll & E.A.F.Ruska constructed the prototype
electron microscope in 1931, capable of four-hundred-power
magnification. https://en.wikipedia.org/wiki/Electron_microscope

Cytology Cell Biology


1943-1944, Oswald T Avery:
DNA is the carrier of genes in cells.
1953, J. Waston & F. Crick (1916-2004,UK):
DNA double helix model.

Molecular cell biology


Rosalind Franklin: The Dark Lady of DNA
An English chemist and X-ray crystallographer who
made contributions to the understanding of the
molecular structures of DNA, RNA, viruses, etc.
https://en.wikipedia.org/wiki/Rosalind_Franklin
The Cell Biology
Time Line
Section 3. Cell Biology and Medicine

The Nobel Prizes in Physiology or Medicine


The 2008 Nobel Prize in Physiology or Medicine was for
the discovery of two viruses (HIV &HPV) causing severe
human diseases. →cervical cancer vaccine

French virologist Francoise Barre-Sinoussi (61years old),


French Professor Luc Montagnier(76) and
German Professor Harald zur Hausen(72).
The 2009 Nobel Prize in Physiology or Medicine was "for
the discovery of how chromosomes are protected by
telomeres and the enzyme telomerase".

Elizabeth H. Carol W. Jack W.


Blackburn Greider Szostak
Robert G. Edwards (1925.6.8—2013.4.10)
Robert G. Edwards was awarded the 2010 Nobel Prize for
the development of human in vitro fertilization (IVF) therapy.
His achievements have made it
possible to treat infertility, a medical
condition afflicting a large
proportion of humanity including
more than 10% of all couples
worldwide.

31
The Nobel Prize in Physiology or Medicine 2011 was
divided, one half jointly to Bruce A. Beutler and Jules A.
Hoffmann "for their discoveries concerning the activation
of innate immunity" and the other half to Ralph M.
Steinman "for his discovery of the dendritic cell and its
role in adaptive immunity".

Bruce A. Beutler Jules A. Hoffmann Ralph M. Steinman


The 2012 Nobel Prize recognized two scientists who
discovered that mature, specialized cells can be
reprogrammed to become immature cells capable of
developing into all tissues of the body. Their findings
have revolutionized our understanding of how cells
and organisms develop.

Sir John B. Gurdon Shinya Yamanaka


The Nobel Prize in Physiology or Medicine 2014 was
divided, one half awarded to John O'Keefe, the other
half jointly to May-Britt Moser and Edvard I. Moser "for
discovering the 'inner GPS' in the brain that helps us
navigate through the world (for their discoveries of
cells that constitute a positioning system in the
brain)".

John O'Keefe May-Britt Moser Edvard I. Moser


Prize share: 1/2 Prize share: 1/4 Prize share: 1/4
The Nobel Prize in Physiology or Medicine 2016 was
awarded to Yoshinori Ohsumi "for his discoveries of
mechanisms for autophagy".

“Professor Ohsumi liked


working on problems that others
stayed away from”.

https://en.wikipedia.org/wiki/Yoshinori_Ohsumi
35
The Nobel Prize in Physiology or Medicine 2018 was
awarded jointly to James P. Allison and Tasuku Honjo
"for their discovery of cancer therapy by inhibition of
negative immune regulation."

Their pioneering work on the


CTLA4 and PD1 immune
checkpoints revealed that these
pathways act as so-called
‘brakes’ on the immune system,
and showed that inhibition of
these checkpoint pathways
allows T cells to more effectively
eradicate cancer cells.
Ligand-receptor interactions between tumor cells
and immune cells in the tumor microenvironment.
The Nobel Prize in Physiology or Medicine 2019 was
for the discoveries of how cells sense and adapt to
oxygen availability.

William G. Kaelin Jr Sir Peter J. Ratcliffe Gregg L. Semenza

38
Warburg effect
Glucose metabolism in normal cells
Changes in glucose metabolism in cancer cells
Animal cells undergo fundamental shifts in gene expression when there are
changes in the oxygen levels around them. These changes in gene expression
alter cell metabolism, tissue remodeling, and even organismal responses such as
increases in heart rate and ventilation. In studies during the early 1990’s, Gregg
Semenza identified, and then in 1995 purified and cloned, a transcription factor
that regulates these oxygen dependent responses. He named this factor HIF, for
Hypoxia Inducible Factor, and showed that it consists of two components: one a
novel and oxygen-sensitive moiety, HIF-1a , and a second, previously identified
and constitutively expressed and non-oxygen-regulated protein known as ARNT.
William Kaelin, Jr. was in 1995 engaged in the study of the von Hippel-Lindau
tumor suppressor gene, and after isolation of the first fulllength clone of the gene
showed that it could suppress tumor growth in VHL mutant tumorigenic cell lines.
Ratcliffe then demonstrated in 1999 that there was an association between VHL
and HIF1a, and that VHL regulated HIF-1a post-translational and oxygen-sensitive
degradation. Finally, the Kaelin and Ratcliffe groups simultaneously showed that
this regulation of HIF-1a by VHL depends on hydroxylation of HIF-1a , a covalent
modification that is itself dependent on oxygen. The combined work thus
demonstrated that the response by gene expression to changes in oxygen is
directly coupled to oxygen levels in the animal cell, allowing immediate cellular
responses to occur to oxygenation through the action of the HIF transcription
factor.
The more we find out about
cells, the more new questions
emerge……

Reference books:
1. Bruce Alberts, Alexander Johnson, Julian Lewis, and
Martin Raff, Molecular Biology of the Cell (5th and 6th
edition), 2010, 2015.
2. Harvey Lodish, Arnold Berk, Chris A. Kaiser, and
Monty Krieger. Molecular Cell Biology (8th edition),
2016.
3.Gerald Karp, Cell and Molecular Biology: Concepts
and Experiments (6th edition), 2010.

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